GdhR is a GntR-type regulator of Neisseria gonorrhoeae encoded by a gene (gdhR) belonging to the MtrR regulon, which comprises multiple genes required for antibiotic resistance such as the mtrCDE efflux pump genes. In previous work we showed that loss of gdhR results in enhanced gonococcal fitness in a female mouse model of lower genital tract infection. Here, we used RNA-Seq to perform a transcriptional profiling study to determine the GdhR regulon. GdhR was found to regulate the expression of 2.3% of all the genes in gonococcal strain FA19, of which 39 were activated and 11 were repressed. Within the GdhR regulon we found that lctP, which encodes a unique L-lactate transporter and has been associated with gonococcal pathogenesis, was the highest of GdhR-repressed genes. By using in vitro transcription and DNase I footpriting assays we mapped the lctP transcriptional start site (TSS) and determined that GdhR directly inhibits transcription by binding to an inverted repeat sequence located 9 bases downstream of the lctP TSS. Epistasis analysis revealed that, while loss of lctP increased susceptibility of gonococci to hydrogen peroxide (H2O2) the loss of gdhR enhanced resistance; however, this GdhR-endowed property was reversed in a double gdhR lctP null mutant. We assessed the effect of different carbon sources on lctP expression and found that D-glucose, but not L-lactate or pyruvate, repressed lctP expression within a physiological concentration range but in a GdhR-independent manner. Moreover, we found that adding glucose to the medium enhanced susceptibility of gonococci to hydrogen peroxide. We propose a model for the role of lctP regulation via GdhR and glucose in the pathogenesis of N. gonorrhoeae.

中文翻译：

---

编码毒力因子（L-乳酸通透酶）的淋球菌基因的转录调控。

GdhR 是淋病奈瑟菌的 GntR 型调节因子，由属于 MtrR 调节子的基因 (gdhR) 编码，该基因包含抗生素抗性所需的多个基因，例如 mtrCDE 外排泵基因。在以前的工作中，我们表明 gdhR 的丧失导致下生殖道感染的雌性小鼠模型中淋球菌适应性增强。在这里，我们使用 RNA-Seq 进行转录分析研究以确定 GdhR 调节子。发现 GdhR 调节淋球菌 FA19 菌株中 2.3% 的所有基因的表达，其中 39 个被激活，11 个被抑制。在 GdhR 调节子内，我们发现 lctP 编码独特的 L-乳酸转运蛋白并与淋球菌发病机制相关，是 GdhR 抑制基因中最高的。通过使用体外转录和 DNase I 足迹分析，我们绘制了 lctP 转录起始位点 (TSS) 并确定 GdhR 通过与位于 lctP TSS 下游 9 个碱基的反向重复序列结合来直接抑制转录。上位性分析表明，虽然 lctP 的丧失增加了淋球菌对过氧化氢 (H2O2) 的敏感性，但 gdhR 的丧失增强了抵抗力；然而，这种 GdhR 赋予的特性在双 gdhR lctP 无效突变体中被逆转。我们评估了不同碳源对 lctP 表达的影响，发现 D-葡萄糖，但不是 L-乳酸或丙酮酸，在生理浓度范围内抑制 lctP 表达，但以 GdhR 独立的方式。此外，我们发现向培养基中添加葡萄糖会增强淋球菌对过氧化氢的敏感性。